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Biomedical subjects

H Redl

Publications and source records attributed to H Redl.

At least 91 records · Page 5Linked to original sources
PubMed1994

Intramedullary pressure changes and fat intravasation during intramedullary nailing: an experimental study in sheep.

In this study, intramedullary reaming and nailing were performed following the insertion of pressure transducers in intact tibias and femora. The femur and tibia were instrumented in 12 sheep (group I) and both tibiae in four (group II). The eight procedures of group II were monitored additionally using echocardiography to detect emboli. Intravasation of fat globules was demonstrated in the blood by the Gurd test and correlated with intramedullary pressure and with echocardiographic monitoring in group II. Medullary nailing was found to be always associated with a severe increase in intramedullary pressure, reaching an average of 1126 mm Hg (304 to 1450 mm Hg) in the tibia and of 753 mm Hg (310 to 1126 mm Hg) in the femur during the first reaming procedures. Particle or fat intravasation was greatest during nail insertion. This phenomenon did not depend on the rise in intramedullary pressure. Our findings indicate that fat and bone marrow intravasation occurs during reaming and nailing in long bones. The maximum embolization of marrow contents demonstrated by echocardiography is seen during nail insertion independent of the changes in intramedullary pressure.

Animals↗
PubMed1994

Pulmonary reaction during intramedullary fracture management in traumatic shock: an experimental study.

Immediate nailing of shaft fractures in severely injured patients causes fat embolization. This method therefore is considered potentially dangerous, since fat intravasation in association with multiple trauma and subsequent endotoxemia might lead to pulmonary dysfunction. We therefore studied the pathophysiologic events of intramedullary nailing in the lungs of sheep with chronic instrumentation including lung lymph fistula. In the 7 animals in group I closed nailing of the intact tibia and femur was performed. Group II (n = 7) animals sustained hypovolemic shock and retransfusion prior to nailing, while group III (n = 11) animals were treated like those in group II and further challenged on the following two days with endotoxin. Group III was compared with group IV (n = 6), in which endotoxin was given only once without additional trauma. Nailing in group I led to a significant increase of the MPAP from 10.8 to 13.8 mm Hg postoperatively (p < 0.05), but no increase in lung permeability. Only additional hypovolemia, retransfusion and nailing as performed in groups II and III showed significant increase of the lymph flow (QI) from 4.4 mL/h to 12.4 mL/h and the protein clearance (Pclear) from 3 to 6.3. A significant difference of the pulmonary permeability between group I and II was only observed postoperatively. There was no difference in the lung response between group III and IV. This ovine study corroborates that although nailing causes a moderate increase in pulmonary pressure, it does not lead to increased lung permeability. Only additional hemorrhagic shock, even when adequately resuscitated, leads to lung disturbance postoperatively. The subsequent endotoxin challenge does not aggravate lung injury.

Animals↗
PubMed1994

A noninvasive functional evaluation following peripheral nerve repair with electromyography in a rat model.

A new bipolar surface electrode array was designed and constructed for a noninvasive "closed" functional evaluation with electromyography following sciatic nerve transection in a rat model. This "closed" method was compared with a conventional one-shot "open" measurement. Nerve conduction velocity and distal latency were calculated. Data obtained from the recordings from different animals as well as from the same animal at different points in time yielded excellent reproducibilities. There is no difference in the mean values whether nerve conduction velocity and distal latency are obtained by "closed" or "open" measurements. Correlation was significant (p < 0.01; rNCV = 0.77, rDL = 0.63) between these two methods. The results lead to the conclusion that the noninvasive functional evaluation with the parameters of nerve conduction velocity and distal latency introduced in the present study could be employed as a reliable method for serial functional evaluations following nerve transection in a long-term study in a rat model.

Animals↗
PubMed1994

Left ventricular dysfunction and acute lung injury induced by continuous administration of endotoxin in sheep.

Sixteen sheep were surgically prepared for chronic study. Seven days later, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) group, n = 10) or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered. Between 1 and 8 h post-LPS, there was a hypodynamic state with low cardiac index (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period, the left ventricular end-systolic pressure-diameter relationship (ESPDR), a sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2; sham 17.2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance index (PVRI) were remarkably increased 1 h after the administration of LPS (PAP:LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS 600 +/- 58; sham 158 +/- 23 dynes x s x cm-5 x m2). The early changes in cardiopulmonary function occurred concomitantly with an elevation in tumor necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS 1382 +/- 266; baseline 82 +/- 20 pg/ml) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increase in CI. The ESPDR continued to fall. By 24 h post-LPS the CI was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to 8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension was maintained for the duration of the LPS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Myocardial function in septic sheep.

There is an ongoing discussion whether the heart is the primary target organ responsible for the development of cardiovascular failure during septic shock as well as its onset. We tried to study the reaction of the heart to sepsis in the early phase of 8 h, using a sublethal model of sepsis in six awake cross-bred Austrian mountain sheep. Sepsis was induced by infusion of a live Escherichia coli suspension at a dose of 5 x 10(7) colony-forming units per kg body weight over 8 h. Standard hemodynamic, hematologic and serum tumor necrosis factor (TNF) measurements were obtained. For evaluation of left ventricular performance we used the following methods, tested in five pilot experiments: 1) The shift of the end-systolic pressure-diameter relation. This was characterized by the calculated shift of the transverse external end-systolic diameter of the left ventricle at a "midrange" end-systolic pressure of 100 mmHg (end-systolic ventricular diameter deviation, ESVDD100). Calculations were performed using a second order regression function of the end-systolic pressure diameter points obtained by variation of afterload by a cuff occluder on the aorta; 2) The shift of the (dP/dt)max over end-diastolic diameter ratio compared to control values estimated by a graphical approach. Mean pulmonary pressure increased from 21 +/- 1 to 36 +/- 2 mmHg in the first hour after starting the E. coli infusion and remained elevated during the entire 8 h observation period. Serum TNF was found to peak 1 hour after start of E. coli infusion and was hardly detectable after 3 hours of bacteremia. Mean aortic pressure showed minor changes (maximum 105 +/- 3 mmHg, minimum 91 +/- 2 mmHg) and there were no statistically significant alterations of the cardiac index. ESVDD100 showed an "oscillatory" reaction in the first phase and a statistically significant decrease of contractility in the second phase (at 4 h). This was confirmed by the graphical method of the (dP/dt)max over end-diastolic diameter ratio. We may therefore conclude that there is no early depression of myocardial function or if so, it may be masked by adrenergic stimulation. In the later phase of the 8 h experiment there is a significantly decreased contractility of the heart. This may be compensated (e.g., "Starling" mechanism or heart rate increase) in this sublethal model.

Animals↗
PubMed1994

Anti-tumor necrosis factor antibody treatment of recurrent bacteremia in a baboon model.

Timely intervention in recurrent episodes of sepsis poses a major problem in intensive care, because the diagnosis is often made after the onset of sepsis, delaying the initiation of treatment. There are only a few animal models that cover this situation. We have developed a baboon model of recurrent bacteremia (3 x 2 h intravenous infusion of 1 x 10(8) CFU Escherichia coli/kg), which leads to late organ failure. In this model (tested on 16 animals) we began anti-tumor necrosis factor antibody treatment (BAYX 1351; Bayer AG, 7.5 mg/kg or saline placebo) after the first bacteremic episode (+4 h), which significantly (p < .05) protected animals from death, none out of eight (100% survival), in the treatment group in contrast to four animals out of eight died (50% survival) in the placebo group. This effect was also reflected in improved organ function and in attenuated cytokine and plasminogen activator inhibitor release. From these studies we conclude that the delayed application of anti-tumor necrosis factor antibodies in recurrent bacteremia is a powerful tool for preventing septic death.

Animals↗
PubMed1994

Similar cytokine but different coagulation responses to lipopolysaccharide injection in D-galactosamine-sensitized versus nonsensitized rats.

To compare cytokine release and coagulation disturbances induced by administration of high versus low doses of endotoxin (lipopolysaccharide [LPS]), we used two endotoxin test systems similar in mortality but different in the degree of endotoxemia. One group of rats (n = 11) randomly received endotoxin (15.0 mg/kg of body weight intraperitoneally [i.p.]) and 1 ml of Ringer's solution (nonsensitized animals). The second group (n = 11) received 1 ml of D-galactosamine (500 mg/kg i.p.) and endotoxin (100 micrograms/kg i.p.) simultaneously (sensitized animals). Endotoxin levels in the plasma of nonsensitized rats were 1,000-fold higher than those in the plasma of sensitized rats (69.33 x 10(3) +/- 22.42 x 10(3) versus 75.8 +/- 27.08 ng of LPS per ml), leading to a mortality of 91% in nonsensitized rats versus 82% in the sensitized-rat model within 48 h postendotoxemia. Serum transaminase activity increased up to 100-fold in sensitized rats as a sign of hepatocyte damage. Despite the large difference in LPS levels in plasma, the time courses of the plasma tumor necrosis factor (TNF) increase were similar in the two groups, with a peak at 2 h (54 +/- 12 ng/ml in nonsensitized rats versus 43 +/- 12 ng/ml in sensitized rats), and also similar to that of a group of nonsensitized rats (n = 5) that received a low dose of LPS (100 micrograms/kg) only (52 +/- 21 ng/ml), while D-galactosamine alone did not induce TNF release. Despite similar TNF levels, a more pronounced coagulation disorder was observed at 4 h in nonsensitized rats (with the high LPS dose) as measured by platelet counts, plasma fibrinogen levels, and activated partial thromboplastin time prolongation (191 x 10(3) +/- 107 x 10(3) cells per microliter, 40 +/- 24 mg/dl, and 53 +/- 15 s, respectively) than in rats with the low LPS dose either sensitized (495 x 10(3) +/- 153 x 10(3), 95 +/- 49, and 38 +/- 16, respectively) or nonsensitized (439 x 10(3) +/- 62 x 10(3), 170 +/- 18, and 35 +/- 11, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Exposure of the hydrophobic components of porcine lung surfactant to oxidant stress alters surface tension properties.

We have tested the hypothesis that oxidation of lung surfactant results in loss of surface tension lowering function. Porcine lung surfactant was exposed to conditions known to cause lipid peroxidation (0.2 mM FeCl2 + 0.1 mM H2O2 or 5 microM CuCl2). Lipid peroxidation was verified by detection of conjugated dienes, thiobarbituric acid reactive substances, fluorescent products, hydroxy alkenals, and loss of unsaturated fatty acids. Exposed samples had significantly diminished surface tension lowering ability in vitro as measured in a bubble surfactometer. Samples exposed to FeCl2 + H2O2 had significantly diminished surface tension lowering ability in vivo as indicated by their reduced ability to improve lung compliance of surfactant-deficient fetal rabbits. Oxidation of phospholipid mixtures with surface tension lowering activity and containing unsaturated acyl groups resulted in partial loss of activity as determined in vitro. These results suggest that the effect of oxidants on lung surfactant function is due, in part, to effects on the phospholipid components and that acute pulmonary inflammation accompanied by oxygen radical production may result in surfactant lipid peroxidation and loss of surface tension lowering function.

Animals↗
PubMed1994

Repeated administration of a F(ab')2 fragment of an anti-tumor necrosis factor alpha monoclonal antibody in patients with severe sepsis: effects on the cardiovascular system and cytokine levels.

In an uncontrolled clinical trial the effects of repeated administration of the F(ab')2 fragment of a murine monoclonal anti-tumor necrosis factor alpha (TNF alpha)-antibody (MAK 195F) on cytokine levels and the cardiovascular system were studied in 20 patients with severe sepsis. Patients were treated with a total of 11 single dosages of the anti-TNF alpha-antibody intravenously over 5 days using either 1 mg/kg (n = 10) or 3 mg/kg (n = 10). The anti-TNF alpha-antibody was well tolerated in all patients without signs of toxicity and without development of anti-murine antibodies. As assessed by cytokine levels (TNF alpha, Interleukin-6) and hemodynamics there was no evidence that the higher dosage of the anti-TNF alpha-antibody (3 mg/kg per dose) was more effective than the lower dosage (1 mg/kg per dose). Comparison of our data with recent data from phase I or II trials using a complete murine monoclonal anti-TNF alpha-antibody suggest that the F(ab')2 fragments of the murine monoclonal anti-TNF alpha-antibody may be of similar efficacy. Definitive conclusions, however, with respect to improvement of mortality and improvement of the cardiovascular system, await the results of larger ongoing placebo-controlled trials.

Adult↗
PubMed1994

Changes in skeletal muscle pO2 after administration of anti-TNF alpha-antibody in patients with severe sepsis: comparison to interleukin-6 serum levels, APACHE II, and Elebute scores.

In 20 patients with severe sepsis, skeletal muscle pO2 was continuously measured in order to assess whether a decrease of skeletal muscle pO2 was accompanied by an improvement of sepsis after repeated administration of F(ab')2 fragments of a murine anti-TNF alpha-antibody. Abnormally high skeletal muscle pO2 decreased from 43.5 +/- 10.9 mmHg (day 0) to 36.4 +/- 10.1 mmHg within 24 h after the first administration of anti-TNF alpha-antibody (day 1, p = .006, n = 20) and remained at 34.6 +/- 7.7 mmHg thereafter (mean day 2-7, p = .004). The decrease of skeletal muscle pO2 within 24 h exceeded 5 mmHg (-7 to -19 mmHg) in 11 patients in contrast to nine patients (-4 to +4 mmHg). Only in the patients showing a decrease of skeletal muscle pO2 did sepsis improve as determined by Elebute score, APACHE II score, and interleukin-6 serum levels. The change of skeletal muscle pO2 within 24 h was associated with a change of interleukin-6 serum levels within 24 h (r = .5, n = 20), with a change of Elebute score (r = .7, n = 20) and of APACHE II score (r = .62). These data suggest that a decrease of skeletal muscle pO2 might be an early indicator of improvement of sepsis after administration of anti-TNF alpha-antibodies.

Adult↗
PubMed1994

Big-endothelin release in baboon bacteremia is partially TNF dependent.

Big-endothelin (big-ET) is one of the endothelium-derived vasoactive substances that plays an important role in regulating the vascular tone. Because the role of this agent in bacteremia remains unknown, we investigated whether bacteremia induces the release of big-ET in a subhuman primate model and whether tumor necrosis factor (TNF) is an important mediator of big-ET release. To study this, we infused 8 male baboons (17 to 19 kg body weight) intravenously for 2 hours with Escherichia coli (5 x 10(8) CFU/kg) and observed them for 72 hours. Plasma was obtained at various intervals and assayed for big-ET by using immunoassay. Four bacteremic animals given vehicle only showed a peak big-ET plasma concentration of 15.1 +/- 4.6 fmol/ml at 10 hours, as compared with a baseline concentration of 0.9 +/- 0.5 fmol/ml. Administration of anti-TNF monoclonal antibodies (CB6, 15 mg/kg) 2 hours before E. coli infusion in additional animals prevented the rise in plasma TNF levels (5.7 +/- 2.5 ng/ml versus nondetectable) and significantly (p < 0.01) attenuated the release of big-ET. Hemodynamic measurements revealed the typical pattern of sepsis, with generally more stable circulatory conditions in the anti-TNF-treated animals. Moreover, the mortality rate decreased from 100% to 0% with anti-TNF treatment. These studies, therefore, lead us to conclude that TNF, directly or indirectly through another mediator, plays an important role in the endothelin production/release during bacteremia and that neutralization of circulating TNF appears to be beneficial for improving the survival after bacteremia.

Animals↗
PubMed1994

Response of the endothelium to trauma and sepsis. Adherence, cytokine effects and procoagulatory response.

Trauma and sepsis induced organ dysfunction is the result of an overwhelming inflammatory response, in which the endothelium plays a central role. Within the mediator cascade reactions involve thrombin, histamine induced endothelial "stimulation" and endotoxin/cytokine induced endothelial "activation" in the endothelial/leukocyte interactions. Adherence events beyond the physiological degree lead to endothelial damage, increase of permeability and result in organ dysfunction. Activated endothelial cells are further involved in cytokine production and they are important actors in the procoagulatory/anticoagulatory balance. The homeostasis is disturbed in the systemic inflammatory response, which leads to a procoagulant state of the endothelium and severe coagulation disorders.

Blood Coagulation↗
PubMed1993

Clinical detection of LPS and animal models of endotoxemia.

The interest in the study of endotoxemia in the clinical area has increased recently as a result of a) improved and simplified endotoxin determination e.g. chromogenic-kinetic microplate methods (also an improved blood sampling tool is available), b) incidence of sepsis has increased due to improvement in early (e.g. posttraumatic) survival, c) interest in and good evidence for gut translocation as a source of endotoxemia, d) agents have developed, which can antagonize endotoxins. There is evidence that patients with positive endotoxin test in the ICU have a higher incidence of organ failure. To study the pathophysiological consequences of endotoxemia and possible ways of intervention animal models are necessary. The choice of the experimental setting depends on the aim of the study e.g. whether prolonged observation is necessary in survival studies or whether hemodynamic variables have to be measured or whether therapeutic agents only crossreact with primates. Since LPS levels are quite low in clinical studies, an important factor for selection of a relevant animal might be LPS sensitivity, or the use of additional sensitization techniques e.g. galactosamine. Another important aspect in this context is whether LPS is given as bolus or infused up to several days. In this review the dose, time, and route of LPS administration is also discussed. For screening purposes rodents are usually used, or sometimes rabbits due to their higher LPS sensitivity. Another very sensitive animal model is the sheep, which can be chronically instrumented and as a specialty allows lung lymph drainage and thus studies of LPS effects on pulmonary permeability. Pigs are used for hemodynamic studies and often in therapeutical studies if species-specificity of the drug tested is not important, in cases where a large animal is necessary. Finally the non-human primates offer a number of advantages due to human-like physiology, due to the cross-reactivity of human assay systems and accordingly also cross-reactivity of human therapeutic agents. While the chimpanzee also shares the LPS sensitivity of humans, baboons are insensitive like rodents. Thus each model serves to provide some useful purpose and the selection must be made to meet the requirements of the specific questions to be asked, with special emphasis of the chosen endotoxin model on relevance for the human sepsis state.

Animals↗
PubMed1993

Interleukin-8 in serum and cerebrospinal fluid from patients with meningococcal disease.

To evaluate the role of interleukin (IL)-8 in meningococcal disease, a solid-phase double-ligand ELISA was used to quantitate IL-8 in sera and cerebrospinal fluid (CSF) from patients with meningococcal meningitis, bacteremia, or both with or without septic shock. IL-8 was demonstrated in sera from 28 of 62 patients; levels were significantly higher in patients with septic shock without meningitis (median, 36.1 ng/mL) than in patients with other manifestations (median, < 0.02 ng/mL), and 4 of 5 patients who died had high levels. IL-8 was detected in all 27 CSF samples. Serum IL-8 levels correlated highly significantly with those of IL-6 (r = .83) and tumor necrosis factor (TNF; r = .64), while the correlations between corresponding CSF levels were less pronounced (r = .43 and r = .38, respectively) but still significant. Serum IL-8 levels were highest in patients with a symptom history < 12 h. The elimination rate of IL-8 from serum varied and was similar to that of IL-6 and TNF. IL-8 appears to participate in the complex cytokine network during the initial phase of systemic meningococcal infections.

Adolescent↗
PubMed1993

Interleukin-8 release in baboon septicemia is partially dependent on tumor necrosis factor.

The role of tumor necrosis factor (TNF) in interleukin (IL)-8 release in septicemia in the baboon (2-h infusion of live Escherichia coli, 5 x 10(8) cfu/kg) was investigated. Four experiments were done: one control (n = 7) and three with pretreatment to reduce TNF plasma levels. Pretreatment was with anti-TNF antibody (anti-TNF) 15 mg/kg, which neutralized circulating TNF (n = 4); 0.5 mg/kg of anti-TNF, which reduced peak TNF from 6.2 ng/mL (controls) to 0.6 ng/mL (n = 4); and a xanthine derivate (HWA138), which reduced TNF to 1 ng/mL (n = 5). With TNF levels < 1 ng/mL, a significant reduction of circulating IL-8 from 10.4 ng/mL (peak) in controls to 1 ng/mL (peak) in anti-TNF-treated animals was found, but with HWA138 only some decrease in IL-8 was seen. Despite high endotoxin levels (10-30 ng/mL peak), neutralization of TNF resulted in diminished release of IL-8 and significantly lower levels of granulocyte elastase.

Animals↗
PubMed1993

Involvement of oxygen radicals in shock related cell injury.

Shock-related organ failure evolves from a variety of starting points--ischemia, reperfusion, non-bacterial or bacterial inflammation--several mechanisms are involved. In addition to the effects of xanthine oxidase after ischemia/reperfusion, toxic oxygen species from phagocytes that accumulate in both intra- and extravascular tissue spaces are of central importance. A critical event is the contact (adhesion) of leukocytes to endothelial cells, which consequently are the targets for leukocyte products. Damage of membranes by lipid peroxidation and by exposure to mediators such as platelet activating factor (PAF), leukotrienes and proteases, leads to increased permeability, tissue oedema and organ dysfunction. Thus antioxidants and other agents that control phagocyte function are likely to contribute to the protection of the permeability barrier in shock states.

Burns↗
PubMed1993

Scoring systems and blood lactate concentrations in relation to the development of adult respiratory distress syndrome and multiple organ failure in severely traumatized patients.

In 56 patients with multiple trauma with ISSs > or = 33 we prospectively collected data of seven scoring systems (ISS, TS, TRISS, GCS, PTS, APACHE II, SSS) and sequentially determined blood lactate concentrations. These data were analyzed in relation to the patients later developing adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Twenty-two patients developed ARDS, and 18 developed MOF. Of the mentioned scoring systems only ISS, PTS, and SSS were predictive of subsequent ARDS, and only ISS and SSS were predictive of subsequent MOF. Lactate concentrations at days 2, 3, and 4 were significantly different between patients with and without subsequent ARDS, MOF, or both. Surprisingly, APACHE II scores did not correlate with subsequent ARDS or MOF, nor did they show any significant relation with lactate concentrations at any time. By stepwise regression analysis ISS, SSS, and lactate level at day 3 were the most significant variables toward the development of ARDS and MOF. It is concluded that scoring systems directly grading the severity of groups of trauma patients have predictive value for late and remote complications such as ARDS and MOF, whereas scoring systems that grade the physiologic response to trauma--although clearly related to mortality--have no such predictive value.

Adolescent↗